A proliferation inducing ligand (APRIL) is one of the most recently cloned members of the tumor necrosis factor (TNF) family. Early experiments implicated a pathophysiological role for APRIL in the promotion of solid tumors. Later, identification of APRIL receptors on B lymphocytes indicated a physiological role for APRIL in humoral responses. We have been able to generate antibodies that detect APRIL protein in human tissues. The study of in situ APRIL expression showed that APRIL mainly regulates late stages of B-cell humoral responses. It also provided evidence that APRIL may modulate tumor development in patients, but only for specific B-cell malignancies. Here, we will review to what extent fine characterization of in situ expression adds valuable information on APRIL (patho) physiological functions.